Shenzhen Kangzhe Pharmaceutical Co.

Shenzhen, China

Shenzhen Kangzhe Pharmaceutical Co.

Shenzhen, China
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Sun Y.-J.,Shenzhen Kangzhe Pharmaceutical Co. | Yu H.-L.,Shenzhen Kangzhe Pharmaceutical Co. | Wei J.,Shenzhen Kangzhe Pharmaceutical Co. | Ding W.-F.,Shenzhen Kangzhe Pharmaceutical Co.
Pharmaceutical Biotechnology | Year: 2010

To study the effect of protease inhibitors on the metabolism and pharmacokinetics of Tyroserleutide, in the serum metabolism system in vitro, four protease inhibitors were separately added into the serum metabolism system in vitro to evaluate the effect on the metabolism curve of Tyroserleutide, and then further evaluate the effect of combination use on the pharmacokinetics of Tyroserleutide. The serum metabolism inhibition test suggests that bestatin significantly inhibits the degradation of Tyroserleutide by serum in vitro. Pharmacokinetics study of Tyroserleutide in rats suggests that aminopeptidase is the main enzyme involved in the degradation of Tyroserleutide. The combination use of bestatin and Tyroserleutide is a promising therapeutic regimen, and need to be investigated in the clinical trial.

Fu Z.,Tianjin Medical University | Ren L.,Tianjin Medical University | Wei H.,Tianjin Medical University | Lv J.,Tianjin Medical University | And 8 more authors.
Journal of Drug Targeting | Year: 2014

Tyroserleutide (YSL) is an active, low-molecular-weight polypeptide with in vitro and in vivo anticancer effects on human hepatocellular carcinoma BEL-7402 cells. In this study, we studied the effects of YSL on PI3K/AKT in the BEL-7402 cells to explore its anti-tumor mechanism. Results showed that YSL could up-regulate the mRNA and protein expression of tumor suppressor PTEN and increase their activities, meanwhile inhibited the mRNA and protein expression of oncogene AKT and decreased the kinase activities of AKT and PDK1. The resuming balance effect of YSL between PTEN and AKT could prevent the transmission of tumor cell proliferation signals in the PI3K/AKT pathway. Inhibition of AKT would change the status of downstream effectors in the PI3K/AKT pathway: (1) inhibition of AKT up-regulated expression of cell cycle regulatory factors of downstream-P21 and P27 which repressed cell cycle and inhibited proliferation of tumor cells. (2) Inhibition of AKT decreased the phosphorylation level of MDM2, and then increased the protein level of P53 which would accelerate death proceeding of tumor cells. (3) Inactivation of AKT removed its inhibition effect on phosphorylation of Bad, which might decrease protein level of apoptosis inhibitor Bcl-2 and Bcl-XL, damaging mitochondria of tumor cells and inducing apoptosis. © 2014 Informa UK Ltd.

Liang H.-Y.,Donghua University | Zhang D.-Q.,Donghua University | Yue Y.,Foshan University | Shi Z.,Shenzhen Kangzhe Pharmaceutical Co. | Zhao S.-Y.,Donghua University
Archiv der Pharmazie | Year: 2010

A series of 1,3-dihydro-2H-3-benzazepin-2-ones with a piperazine moiety were designed and synthesized by treating the common intermediate of 1,3-dihydro-7,8-dimethoxy-3-[3-(1-piperazinyl)-propyl]-2H-3-benzazepin-2-ones with a variety of N-aryl-2-chloroacetamides and acyl chlorides. Their structures have been characterized by 1H-NMR, MS, and elemental analysis. The title compounds were evaluated for their bradycardic activity in vitro. Most of the synthesized compounds exhibited some vasorelaxant activity and heart-rate-reducing activity with bradycardic potency. © 2010 WILEY-VCH Verlag GmbH & Co. KGaA.

Huang Y.-T.,Tianjin Medical University | Zhao L.,Tianjin Medical University | Fu Z.,Tianjin Medical University | Zhao M.,Tianjin Medical University | And 10 more authors.
Drug Design, Development and Therapy | Year: 2016

Tyroservatide (YSV) can inhibit the growth and metastasis of mouse lung cancer significantly. This study investigated the therapeutic effects of tripeptide YSV on metastasis of human lung cancer cells and explored its possible mechanism that affects integrin–focal adhesion kinase (FAK) signal transduction in tumor cells. YSV significantly inhibited the adhesion and the invasion of highly metastatic human lung cancer cell lines 95D, A549, and NCI-H1299. In addition, YSV significantly inhibited phosphorylation of FAK Tyr397 and FAK Tyr576/577 in the 95D, A549, and NCI-H1299 human lung cancer cells in vitro. And the mRNA level and protein expression of FAK in these human lung cancer cells decreased at the same time. YSV also significantly inhibited mRNA and protein levels of integrin β1 and integrin β3 in the 95D, A549, and NCI-H1299 human lung cancer cells. Our research showed that YSV inhibited adhesion and invasion of human lung cancer cells and exhibited therapeutic effects on metastasis of lung cancer. © 2016 Huang et al.

Li Y.,China Pharmaceutical University | Li Y.,Shenzhen Kangzhe Pharmaceutical Co. | Yang H.,National Institutes for Food and Drug Control NIFDC | Liao H.,National Institutes for Food and Drug Control NIFDC | And 4 more authors.
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2013

A selective and sensitive ultra-performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-MS) method was developed for the simultaneous determination of ten biogenic amines (tryptamine, 2-phenylethylamine, putrescine, cadaverine, histamine, tyramine, spermidine, adrenaline, dopamine and spermine) in a thymopolypeptides injection from the Chinese market for the first time. Biogenic amines (BAs) were pre-column derivatised by dansyl chloride after direct sample dilution. Dansylated amines were separated on an ACQUITY UPLC BEH Shield RP18 column (2.1. mm. ×. 150. mm I.D., 1.7. μm) using a gradient elution. Quantification was done by monitoring fragment ions of each derivative under the MS mode of multiple reaction monitoring (MRM). A satisfactory result of method validation was obtained. The linearity ranged from 0.32 to 1182.9. μg/L and the correlation coefficients (r) for all amines were above 0.99. The LOD ranged from 0.08. μg/L for 2-phenylethylamine and tyramine to 8.00. μg/L for adrenaline; the LOQ ranged from 0.32. μg/L for 2-phenylethylamine to 12.12. μg/L for dopamine. The recovery ranged from 75.8 to 110.3% after spiking standard solutions of BAs to a sample at three levels. The intra and inter-day precision RSD were 0.78-8.85% and 1.39-9.93% respectively. Eighty-four injections were analyzed by this method. Nine biogenic amines were found in them except adrenaline. Moreover, the relationship between the result of test for depressor substances and the content of BAs was statistically analyzed. © 2013 Elsevier B.V.

Jia J.-B.,Fudan University | Jia J.-B.,Shenzhen Kangzhe Pharmaceutical Co. | Wang W.-Q.,Fudan University | Sun H.-C.,Fudan University | And 11 more authors.
Investigational New Drugs | Year: 2011

Previous studies have demonstrated that tyroserleutide (YSL) inhibits tumor growth in an animal model of hepatocellular carcinoma (HCC). However, its effects on HCC metastasis are still not fully understood. To examine YSL as a novel agent to prevent HCC metastasis, a metastatic human HCC orthotopic nude mouse model of MHCC97L was used. The antitumor and antimetastasis effects of YSL were also evaluated in combination with radiation. Hypoxia and epithelial-mesenchymal transition (EMT)-related molecules were studied. YSL inhibited MHCC97L cell invasion in vitro with or without irradiation. YSL did not significantly inhibit tumor growth but decreased pulmonary metastasis and prolonged life-span for more than 40 days, which correlated with down-regulation of matrix metalloproteinase-2. Radiotherapy inhibited early-stage tumor growth and promoted tumor hypoxia. The re-implanted tumor volume in the radiotherapy group was not significantly different from the control, in which the incidence of lung metastasis increased after radiotherapy (6/6 versus 3/6, P=0.046); however, YSL inhibited the growth of re-implanted tumor after radiotherapy. Furthermore, YSL at 160 or 320 μg/kg/day almost completely inhibited lung metastasis induced by irradiation (1/6 versus 6/6, P=0.002 for both dosages). YSL down-regulated hypoxia-inducible factor 1α (HIF-1α) and transmembrane protease serine 4 ( ™PRSS4), and inhibited EMT was associated with the antimetastasis capability of YSL. Our data suggest that YSL inhibits the enhanced invasiveness and metastatic potential of HCC induced by irradiation through down-regulation of HIF-1α and ™PRSS4 and inhibition of EMT. YSL may have potential as a new antimetastasis agent for radiotherapy. © Springer Science+Business Media, LLC 2010.

Che X.,Tianjin Medical University | Hu J.,Tianjin Medical University | Lin G.,Shenzhen Kangzhe Pharmaceutical Co. | Lu R.,Tianjin Medical University | And 3 more authors.
Molecular and Cellular Biochemistry | Year: 2011

Peptide deformylase (PDF) is considered an attractive target for screening novel antibiotics. The PDF from Escherichia coli and Staphylococcus aureus are representative of the gram-negative species type of PDF (type I PDF) and the gram-positive species type of PDF (type II PDF), respectively. They could be used for screening broad-spectrum antibiotics. Herein, we cloned the def gene by PCR, inserted it into plasmid pET-22b-def, and transformed the plasmid into E. coli BL21 (DE3) cells, then the cells were induced by IPTG to express PDF. E. coli Ni2+-PDF was extracted and purified by ion-exchange chromatography and gel filtration chromatography. S. aureus PDFs were extracted and purified using the MagExtractor kit. The nickel form of S. aureus PDF was obtained by adding NiCl2 to all reagents used for purification. Iron-enriched S. aureus PDF was obtained by adding FeCl3 to the growth medium for E. coli BL21 (DE3) cells and adding FeCl3 and catalase to all reagents used for purification. The activities of PDFs were analyzed, compared, and grouped according to the experimental conditions that produced optimal activity, and we used actinonin as an inhibitor of PDF and calculated the IC50 value. We obtained high expression of E. coli and S. aureus PDF with high activity and stability. The function of PDFs was inhibited by actinonin in a dosedependent manner. Results may be helpful for future mechanistic investigations of PDF as well as high-throughput screening for other PDF inhibitors. © Springer Science+Business Media, LLC. 2011.

Wang L.,Tianjin Medical University | Wang S.,Tianjin Medical University | Lu R.,Tianjin Medical University | Lu R.,Shenzhen Kangzhe Pharmaceutical Co. | And 10 more authors.
Transplant Immunology | Year: 2010

The pentapeptide PLNPK (Pro-Leu-Asn-Pro-Lys) is extracted from the spleen. Preliminary studies have shown that PLNPK could inhibit T lymphocyte transformation and antibody production. In the present study, we detected the inhibitory effect of PLNPK on one-way mixed leukocyte reaction (MLR) in vitro and observed the effect of PLNPK on the duration of allograft survival in mouse models of skin or cardiac transplantation. Pathological damage and T cell infiltration of the grafts were also detected. Results showed that PLNPK could significantly inhibit T lymphocyte proliferation, with an optimized inhibition of 40%. Also PLNPK could significantly prolong the mean survival time of skin allograft and cardiac allograft, producing survival rates of 42% and 38.7%, respectively. PLNPK at a dose of 200 μg/kg/d or 100 μg/kg/d could significantly suppress ConA-induced T cell proliferation and T cell IL-2 secretion in transplant recipient mice, compared to the saline group (P<0.05). This information suggests that PLNPK can effectively antagonize transplant rejection, possibly by reducing IL-2 secretion by T cells and inhibiting T cell proliferation and activation. © 2010 Elsevier B.V.

Jian X.,Tianjin Medical University | Fu Z.,Tianjin Medical University | Zhang Y.,Tianjin Medical University | Che X.,Tianjin Medical University | And 2 more authors.
Experimental and Therapeutic Medicine | Year: 2012

Tyroserleutide (YSL) is a tripeptide compound that exhibits potent antitumor activity in human tumor xenografts and tumor cell lines. However, the target of YSL on which it exerts its antitumor activity has yet to be identified. Therefore, our study aimed to investigate the subcellular location of YSL in BEL-7402 human hepatocellular carcinoma cells. Using methods of fluorescent tracing and confocal colocalization, we provide evidence that when BEL-7402 cells are treated with YSL, YSL is distributed in the cytoplasm and colocalized with the mitochondria of cancer cells. Furthermore, we observed the effect of YSL on the isolated mitochondria. Using fluorescence spectrophotometry to monitor the Δψ collapse of mitochondria isolated from BEL-7402 cells by reversion of the quenching of tetramethylrhodamine methyl ester (TMRM), we found that the isolated mitochondria reversed the quenching of the fluorescence in the solution containing TMRM and YSL. This indicates that YSL decreases the Δψ of the isolated mitochondria. Another photometry method was used to observe the effect on mitochondrial swelling when YSL acted directly on the isolated mitochondria. We reveal that YSL directly causes mitochondrial swelling in 60 min. In conclusion, this study encloses a preliminary facet of the pharmacological target of YSL, and we speculate that YSL may act directly on the mitochondria to exert its antitumor activity.

Xu Q.,Tianjin Medical University | Lu R.,Tianjin Medical University | Lu R.,Shenzhen Kangzhe Pharmaceutical Co. | Zhu Z.-F.,Tianjin Medical University | And 7 more authors.
International Journal of Cancer | Year: 2011

Tyroservatide (YSV) is an active, low-molecular weight polypeptide shown to have antitumor effects on experimental hepatocarcinoma and lung carcinoma. The focus of our study was to observe the effects of YSV on several human lung carcinoma cell lines and explore its antitumor mechanism via its effect on histone acetylation. Our results showed that YSV significantly inhibited the proliferation of human lung carcinoma A549, NCIH460, NCIH292 and NCIH1299 cells, induced G0/G1 cell cycle arrest and increased protein and mRNA levels of p21 and p27. Moreover, YSV treatment significantly inhibited histone deacetylase (HDAC) activity and resulted in the accumulation of acetylated histones H3 and H4 in total cellular chromatin and p21 gene-associated chromatin regions. Together these data suggest that the antitumor effects of YSV might be mediated by its inhibition of HDAC activity, selectively upregulating the expression of p21 by increasing the acetylation of histones associated with p21 gene regions, resulting in an induction of G 0/G1 cell cycle arrest and inhibition of the proliferation of tumor cells. Our findings demonstrate that YSV may exhibit potent therapeutical effects on lung carcinoma. Copyright © 2010 UICC.

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